Document Detail


Comparison of the effects of the superoxide dismutase mimetics EUK-134 and tempol on paraquat-induced nephrotoxicity.
MedLine Citation:
PMID:  17640563     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paraquat-induced nephrotoxicity involves severe renal cell damage caused by reactive oxygen species (ROS), specifically via increasing concentrations of superoxide anions in the kidney. Recently, superoxide dismutase (SOD) mimetics (SODm) have been developed that display safe SOD activities but which also possess additional antioxidant enzyme (e.g., catalase) or ROS-scavenging activities. The aim of this study was to compare the effects of two such SODm, specifically, EUK-134, a SODm with catalase activity, and tempol, a SODm with ROS-scavenging properties, on paraquat-induced nephrotoxicity of renal NRK-52E cells. Incubation with paraquat (1 mM) for 24 h reduced cell viability and increased necrosis significantly. Paraquat also generated significant quantities of superoxide anions and hydroxyl radicals. Both EUK-134 (10-300 microM) and tempol (0.3-1.0 mM) were able to improve cell viability and reduced paraquat-induced cell death significantly via dismutation or scavenging of superoxide anions and reduced hydroxyl radical generation. The data presented here suggest that SODm such as EUK-134 and tempol, which possess additional catalase and/or ROS-scavenging activities, can significantly reduce renal cell damage caused by paraquat. These effects were evident at concentrations which avoid the pro-oxidant activities associated with higher concentrations of SOD. Such SODm could therefore prove to be beneficial as therapies for paraquat nephrotoxicity.
Authors:
Mohamed Samai; Martyn A Sharpe; Paul R Gard; Prabal K Chatterjee
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2007-05-16
Journal Detail:
Title:  Free radical biology & medicine     Volume:  43     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-20     Completed Date:  2007-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  528-34     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Therapeutics, University of Brighton, Brighton BN2 4GJ, East Sussex, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*
Cyclic N-Oxides / pharmacology*
Free Radical Scavengers / pharmacology*
Herbicides / toxicity
Hydroxyl Radical / metabolism
Kidney / drug effects*
Kidney Diseases / chemically induced,  drug therapy
Organometallic Compounds / pharmacology*
Paraquat / toxicity*
Rats
Reactive Oxygen Species / metabolism
Salicylates / pharmacology*
Spin Labels
Superoxide Dismutase / metabolism,  pharmacology
Superoxides / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cyclic N-Oxides; 0/EUK-134; 0/Free Radical Scavengers; 0/Herbicides; 0/Organometallic Compounds; 0/Reactive Oxygen Species; 0/Salicylates; 0/Spin Labels; 11062-77-4/Superoxides; 2226-96-2/tempol; 3352-57-6/Hydroxyl Radical; 4685-14-7/Paraquat; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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